Raj D. Sheth

Effect of carbamazepine and valproate on bone mineral density

OBJECTIVE To examine the effect of carbamazepine and valproate monotherapy on bone mineral density in children. METHODS Axial (second, third, and fourth lumbar vertebrae) and appendicular (distal third of radius) bone mineral density was measured by dual-energy x-ray absorptiometry in 27 healthy children and 26 children with uncomplicated idiopathic epilepsy treated with either carbamazepine (n = 13) or valproate (n = 13) for more than 18 months. Control subjects and patients were similar with respect to age, race (all white), and geographic area, and had no dietary restrictions, neurologic impairment, or physical handicaps. RESULTS Subjects were seizure-free for more than 6 months on a regimen of carbamazepine or valproate therapy, and had mean serum trough levels of 6.88 +/- 2 micrograms/ml and 72.04 +/- 45.6 micrograms/ml, respectively. Dietary calcium intake was similar in control and treated groups. After correction for gender and age, children treated with valproate had a 14% (p = 0.003) and 10% (p = 0.005) reduction in bone mineral density at the axial and appendicular sites, respectively. The reduction in bone mineral density increased with the duration of valproate therapy. Carbamazepine did not significantly reduce bone mineral density. CONCLUSION Valproate montherapy, but not carbamazepine therapy, significantly reduces axial and appendicular bone mineral density in children with idiopathic epilepsy and may increase their risk of osteoporotic fractures.

The nature and course of neuropsychological morbidity in chronic temporal lobe epilepsy

Objective: To characterize the nature and degree of cognitive morbidity in patients with chronic temporal lobe epilepsy compared with healthy control subjects, determine the association between the duration of epilepsy and cognitive morbidity, and ascertain whether there are factors that moderate the association between duration of disorder and cognitive impairment. Methods: Temporal lobe epilepsy (n = 96) and healthy control (n = 82) subjects were assessed with a comprehensive neuropsychological battery. Test performances were adjusted for age, gender, and education and transformed to a common metric (z scores). Analyses included group comparisons and correlations of duration of epilepsy with cognitive morbidity. Results: Patients with temporal lobe epilepsy exhibited not only worse memory function (p < 0.05) but worse performance across measures of intelligence, language, executive function, and motor speed (p < 0.05). Chronicity of epilepsy was related to worsening mental status (r = 0.42, p < 0.001). This relationship was particularly evident among those individuals with less (r = 0.58, p < 0.001) compared with more (r = 0.25, NS) cerebral reserve, operationally defined by years of formal education. Conclusions: Neuropsychological morbidity in chronic temporal lobe epilepsy is widespread in nature despite a focal epileptic process. Cross-sectional analyses demonstrate that increasing duration of epilepsy is associated with worsening mental status. Individuals with less educational attainment (low cerebral reserve) exhibit especially poor cognitive function in association with chronicity of epilepsy.

The Neurodevelopmental Impact of Childhood‐onset Temporal Lobe Epilepsy on Brain Structure and Function

Summary:  Purpose: To characterize the neurodevelopmental correlates of childhood‐onset temporal lobe epilepsy on brain structure and cognition compared with late‐onset chronic temporal lobe epilepsy and healthy controls.

Psychiatric comorbidity in children with new onset epilepsy

The aim of this study was to characterize the distribution, timing, and risk factors for psychiatric comorbidity in children with recent onset epilepsy. Children aged 8 to 18 years with recent onset epilepsy (<1 year in duration) of idiopathic etiology (n=53) and a healthy comparison group (n=50) underwent a structured psychiatric diagnostic interview to characterize the spectrum of lifetime‐to‐date history of comorbid psychiatric disorder. There was no significant difference between the children with recent onset epilepsy and healthy comparison children in sex (31 males, 22 females vs 23 males, 27 females) or mean age 12.7y [SD 3.3] vs 12.7y [SD 3.2]). Children with recent onset epilepsy exhibited an elevated rate of lifetime‐to‐date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM‐IV) Axis I disorders compared with the comparison group. They showed significantly higher rates of depressive disorders (22.6 vs. 4%, p=0.01), anxiety disorders (35.8 vs 22%, p<0.05), and attention‐deficit‐hyperactivity disorder (26.4 vs 10%, p=0.01) with elevated but less prevalent rates of oppositional defiant and tic disorders. A subset of children with epilepsy (45%) exhibited DSM‐IV Axis I disorders before the first recognized seizure, suggesting the potential influence of antecedent neurobiological factors that remain to be identified. The increased prevalence of psychiatric comorbidity antedating epilepsy onset may be consistent with the presence of underlying neurobiological influences independent of seizures, epilepsy syndrome, and medication treatment.

Refractory status epilepticus Response to ketamine

Mortality and morbidity associated with status epilepticus (SE) are, to a large extent, determined by the etiology underlying SE and the rapidity with which seizures are controlled.1 Most patients with SE will respond to aggressive treatment protocols that include repeated high doses of phenytoin, phenobarbital, and benzodiazepine. SE refractory to standard treatment protocols may respond to alternative therapies with IV lidocaine or valproic acid, or to continuous infusion of midazolam lorazepam or propofol.2 When these measures fail to control SE, patients may require the induction of coma with pentobarbital.3 A 13-year-old girl with seizures refractory to standard SE protocols, alternative therapeutic strategies, and 4 weeks of pentobarbital coma achieved control of both clinical and electrographic seizures after the administration of ketamine. Case report. A previously healthy 13-year-old girl presented with a 3-day history of muscle aches, fever, and generalized tonic-clonic seizures. She was treated with IV diazepam and loaded with 20 mg/kg phenytoin. SE persisted, and the patient was subsequently loaded with 20 mg/kg phenobarbital. Her seizures persisted despite these measures. Repeated doses of phenobarbital and phenytoin and continuous IV infusion to a maximum dose of 2 mg/kg/hour were ineffective. During the next 12 hours she continued to …

Thalamofrontal circuitry and executive dysfunction in recent-onset juvenile myoclonic epilepsy.

Purpose:  Thalamofrontal abnormalities have been identified in chronic primary generalized epilepsy, specifically in juvenile myoclonic epilepsy (JME). These regions also underlie executive functioning, although their relationship has yet to be examined in JME. This study examined the relationship between thalamic and frontal volumes and executive function in recent‐onset JME compared to healthy control subjects and recent‐onset benign childhood epilepsy with centrotemporal spikes (BCECTS), a syndrome not typically associated with thalamocortical or executive dysfunction.

Growing up with epilepsy: A two‐year investigation of cognitive development in children with new onset epilepsy

Purpose:  To characterize patterns and determinants of normal and abnormal cognitive development in children with new onset epilepsy compared to healthy controls.

Parietal Occipital Edema in Hypertensive Encephalopathy: A Pathogenic Mechanism

Eight patients with hypertensive encephalopathy from diverse etiologies developed cerebral edema in the vertebrobasilar distribution which resolved after blood pressure was lowered. Parietal occipital edema is a recognized feature of hypertensive encephalopathy. The explanation for this regional pathological variation in hypertensive encephalopathy remains undefined. Some evidence suggests that sympathetic innervation of the anterior cerebral vasculature may be protective, and conversely, the relative lack of sympathetic innervation in the vertebrobasilar vasculature may predispose the parietal occipital region to the development of cerebral edema in hypertensive encephalopathy.

Extratemporal quantitative MR volumetrics and neuropsychological status in temporal lobe epilepsy.

Neuropsychological studies of temporal lobe epilepsy have focused heavily on the nature and extent of memory dysfunction and its relationship to the neuropathological status of the hippocampus and related mesial temporal lobe structures. In this study, we examined whole brain and lobar quantitative MRI volumes and comprehensive neuropsychological performance in 58 patients with temporal lobe epilepsy and 62 healthy controls in order to determine (1) the nature and degree of extratemporal structural abnormalities in localization-related temporal lobe epilepsy: (2) the nature and degree of cognitive abnormalities outside of anterograde memory function; and (3) the relationship of volumetric abnormalities to neuropsychological status. Temporal lobe epilepsy patients exhibited significant reduction in the volume of adjusted (age, gender, height) total cerebral tissue (-5.8%), more evident in white (-9.8%) compared to gray matter (-3.0%) tissue volumes. Significant volumetric reductions were evident across frontal, temporal and parietal but not occipital lobe regions. Subarachnoid but not total ventricular CSF was significantly increased in epilepsy patients. Neuropsychological abnormality was generalized in nature, consistent with the generalized nature of the morphometric abnormalities, and reductions in cerebral tissue volumes were directly associated with poorer cognitive performance. In summary, patients with temporal lobe epilepsy exhibited clinically significant structural and functional abnormalities that extended outside the epileptogenic temporal lobe. The degree to which these structural and cognitive abnormalities are due to factors that cause the epilepsy, as opposed to reflecting the consequences of chronic epilepsy (e.g., duration and severity of epilepsy), remain to be determined.

Comorbid Psychiatric Symptoms in Temporal Lobe Epilepsy: Association with Chronicity of Epilepsy and Impact on Quality of Life

Purpose. The goals of this work were to determine: (1) the nature and extent of differences in self-reported psychiatric symptoms between patients with temporal lobe epilepsy and matched healthy controls, (2) the relationship between chronicity (duration) of temporal lobe epilepsy and comorbid interictal psychiatric symptoms, and (3) the impact of comorbid psychiatric symptoms on self-reported health-related quality of life. Methods. Patients with temporal lobe epilepsy (n = 54) and healthy controls (n = 38) were administered the Symptom Checklist-90-Revised (SCL-90-R) to assess the nature and severity of psychiatric symptomatology and epilepsy patients completed the Quality of Life in Epilepsy-89 (QOLIE-89) to define health-related quality of life. Among epilepsy patients the SCL-90-R scales were examined in relation to chronicity of temporal lobe epilepsy as well as the impact of comorbid emotional-behavioral distress on health-related quality of life. Results. Compared with healthy controls, patients with epilepsy exhibited significantly higher (worse) scores across all but one of the 12 SCL-90-R scales. Among patients with epilepsy, increasing chronicity was associated with significantly higher (worse) scores across all SCL-90-R scales and increased emotional-behavioral distress was associated with lower (worse) scores across all 17 QOLIE-89 scales. Conclusion. Comorbid interictal psychiatric symptoms are elevated among patients with temporal lobe epilepsy compared with healthy controls and appear to be modestly associated with increasing chronicity (duration) of epilepsy. This comorbid emotional-behavioral distress is specifically associated with a significantly poorer health-related quality of life, and suggests that quality-of-life research should devote greater attention to the potential impact of comorbid psychiatric distress.